A multivalent bcr-abl fusion peptide vaccination trial in patients with chronic myeloid leukemia Journal Article

Authors: Cathcart, K.; Pinilla-Ibarz, J.; Korontsvit, T.; Schwartz, J.; Zakhaleva, V.; Papadopoulos, E. B.; Scheinberg, D. A.
Article Title: A multivalent bcr-abl fusion peptide vaccination trial in patients with chronic myeloid leukemia
Abstract: A tumor-specific, bcr-abl-derived fusion peptide vaccine can be safely administered to patients with chronic myelogenous leukemia (CML) and can elicit a bcr-abl peptide-specific T-cell immune response. In the present phase 2 trial, 14 patients with CML in chronic phase were vaccinated with 6 fusion peptides mixed with Quillaja saponaria (QS-21). No significant toxic effects were observed. In 14 of 14 patients, delayed-type hypersensitivity (DTH) and/or CD4 proliferative responses developed after beginning vaccinations, and 11 of 14 patients showed interferon-gamma (IFN-gamma) release by CD4 enzyme-linked immunospot (ELISPOT) at one or more time points. These responses were CD4 +CD45RO+. A peptide-specific CD8+ interferon-gamma ELISPOT was found in 4 patients. Four patients in hematologic remission had a decrease in Philadelphia chromosome (Ph) percentage (3 concurrently receiving interferon-alpha and 1 on imatinib mesylate), and 3 patients in molecular relapse after allogenic transplantation became transiently polymerase chain reaction (PCR) negative after vaccination; 2 of these patients received concurrent donor lymphocyte infusion (DLI). All 5 patients on IFN-alpha ultimately reached a complete cytogenetic remission. In conclusion, a tumor-specific bcr-abl breakpoint peptide-derived vaccine can be safely administered and can reliably elicit measurable peptide-specific CD4 immune responses, including in patients after bone marrow transplantation, on interferon, or on imatinib mesylate. A relationship between the clinical responses and vaccination cannot be determined from this trial. © 2004 by The American Society of Hematology.
Keywords: adult; clinical article; middle aged; unclassified drug; hydroxyurea; clinical trial; combined modality therapy; cytarabine; flow cytometry; polymerase chain reaction; cd8 antigen; lymphocyte proliferation; t lymphocyte; edema; pain; phase 2 clinical trial; relapse; cytogenetics; allogenic bone marrow transplantation; chronic myeloid leukemia; chill; dizziness; pruritus; lymphocyte activation; immune response; gamma interferon; cancer vaccines; cd4-positive t-lymphocytes; vaccination; erythema; remission; safety; plant extract; bcr abl protein; liver function test; cd4 antigen; th1 cell; enzyme linked immunospot assay; cd45 antigen; vaccine; fusion proteins, bcr-abl; vaccines, subunit; philadelphia 1 chromosome; delayed hypersensitivity; quillaja; hypersensitivity, delayed; quillaja saponaria extract; quillaja saponaria; interferon type ii; anagrelide; leukemia, myeloid, chronic; humans; human; male; female; priority journal; article
Journal Title: Blood
Volume: 103
Issue: 3
ISSN: 0006-4971
Publisher: American Society of Hematology  
Date Published: 2004-02-01
Start Page: 1037
End Page: 1042
Language: English
DOI: 10.1182/blood-2003-03-0954
PROVIDER: scopus
PUBMED: 14504104
Notes: Blood -- Cited By (since 1996):129 -- Export Date: 16 June 2014 -- CODEN: BLOOA -- Source: Scopus
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